Endocrine Treatment Toxicity in Breast Cancer: A Good Thing?

Specific adverse effects were associated with treatment benefit, but further confirmation is needed.


Recent studies have shown that in postmenopausal women with hormone-receptor–positive breast cancer, the benefits of adjuvant endocrine therapy seem to be associated with the adverse effects of the treatment (e.g., Lancet Oncol 2008; 9:1143).

To examine this association further, investigators conducted a phase III, multinational, open-label, randomized study of 9766 postmenopausal women with estrogen-receptor–positive or progesterone-receptor–positive breast cancer who were eligible for adjuvant endocrine treatment. Patients received either the aromatase inhibitor (AI) exemestane (25 mg daily for 5 years) or tamoxifen (20 mg daily for 2.5–3 years), followed by exemestane (25 mg daily for 2.5–2 years; sequential regimen).

Patients who reported vasomotor symptoms during the first year of treatment achieved longer disease-free survival (DFS) and longer overall survival (OS) than those who did not experience those symptoms. Women who reported musculoskeletal symptoms also achieved superior DFS but not OS. These findings were independent of endocrine therapy assignment.

Comment: These findings of a correlation between toxicity and treatment benefit are intriguing. However, other large studies have reported discordant results (e.g., J Clin Oncol 2011; 29:51s). Only by prospectively controlling for baseline symptoms, concurrent medications, and treatment adherence and by capturing toxicity with validated instruments can a link between adverse effects and treatment success be confirmed. Until then, the search for a biomarker that can identify patients most likely to benefit from adjuvant therapy remains.

Source: Journal Watch Oncology and Hematology




Subclinical Atrial Fibrillation Is Common in Patients with Cryptogenic Stroke.

An implantable loop recorder established new diagnoses of atrial fibrillation in 25% of patients with cryptogenic stroke.

One third of ischemic strokes remain cryptogenic even after thorough inpatient evaluation. Numerous studies suggest that some of these patients may have paroxysmal atrial fibrillation (AF) that remains undiagnosed during their stroke hospitalization. Failing to detect these cases of AF may result in suboptimal antithrombotic therapy. However, what type and duration of cardiac monitoring should be used to rule out subclinical AF remain unclear.

To address this question, investigators placed implantable loop recorders (ILRs) in 51 patients who had received standard stroke evaluations, including vascular imaging, echocardiography (transthoracic in all patients and transesophageal in 30), and at least 24 hours of Holter monitoring without evidence of AF. The ILR software automatically detected AF episodes 2 minutes in duration. Two cardiologists independently reviewed any AF episodes detected by ILRs.

ILRs were implanted an average of 174 days after stroke. In 13 patients (25.5%), AF was detected after a median 48 (range, 0–154) days of monitoring. The other patients remained AF-free throughout an average 229 days of monitoring. AF was associated with older age, more-frequent premature atrial contractions during baseline Holter monitoring, and larger left atrial size.

Comment: In the recently completed EMBRACE trial, 15% of cryptogenic stroke patients assigned to 30-day external loop recorder monitoring received new diagnoses of atrial fibrillation, versus 3% of patients assigned to 24-hour outpatient Holter monitoring. It is possible but unlikely that some of these poststroke episodes of AF are incidental, because subclinical AF lasting only a few minutes has recently been shown to increase stroke risk, and the majority of cryptogenic strokes appear radiographically to have resulted from cardiac embolism. On these bases, several weeks of noninvasive cardiac monitoring should usually be performed in patients with cryptogenic stroke. The current study results suggest that longer periods of monitoring might detect even more cases of AF. However, relatively invasive and expensive implantable loop recorders cannot be routinely recommended until we see the results of the ongoing CRYSTAL-AF trial, which is comparing use of ILRs to routine clinical follow-up in patients with cryptogenic stroke.


Source:Journal Watch Neurology

The #1 WORST Food that HARMS Your Brain.


Two One-Pill Regimens Face Off.

The integrase-based option performed as well as the old efavirenz-based standby.


Now that three single-tablet regimens are available for HIV treatment, competition for the “best” option is intense. In phase III trials comparing efavirenz/FTC/tenofovir (Atripla) and elvitegravir/cobicistat/FTC/tenofovir (Stribild), the two regimens were equally safe and efficacious at week 48 (JW AIDS Clinical Care Jul 9 2012). Longer-term results from one of these trials are now available. The study was sponsored by the maker of elvitegravir/cobicistat/FTC/tenofovir.

Seven hundred treatment-naive HIV-infected patients with genotype-confirmed viral susceptibility to efavirenz, tenofovir, and FTC were randomized to receive either elvitegravir/cobicistat/FTC/tenofovir or efavirenz/FTC/tenofovir along with a placebo version of the other. At week 96, the rates of virologic suppression were similar between groups (84% for elvitegravir/cobicistat/FTC/tenofovir and 82% for efavirenz/FTC/tenofovir), as were the rates of virologic failure (6% and 8%). CD4-cell counts increased similarly in the groups.

Overall rates of adverse events were also comparable, with nausea more common in the elvitegravir/cobicistat/FTC/tenofovir group, neuropsychiatric events more common in the efavirenz/FTC/tenofovir group, and rates of treatment-limiting side effects similar between groups (5% and 7%, respectively). Treatment-limiting renal toxicity from cobicistat was seen in two patients during the second 48 weeks of treatment.

Overall rates of genotypic resistance in patients with virologic failure were similar; most participants with failure on elvitegravir/cobicistat/FTC/tenofovir had developed integrase-resistance mutations, and most of those with failure on efavirenz/FTC/tenofovir had the K103N nonnucleoside reverse transcriptase inhibitor–resistance mutation.

Comment: By all the usual standards, efavirenz and elvitegravir/cobicistat perform equally well for initial antiretroviral therapy, at least when combined with FTC/tenofovir. The high efficacy rates seen with both options is doubtless testimony to their tolerability and to the good adherence seen with single-dose regimens.

Source: Journal Watch HIV/AIDS Clinical Care

HIV cure months away, Danish scientists say, citing novel new DNA treatment.

dna_test_twinsDanish scientists believe they may have a cure for HIV “within months.”

Danish scientists believe they may have a cure for HIV “within months.”

Researchers at Aarhus University Hospital in Denmark are testing a new technique that involves flushing the virus from so-called reservoirs in human DNA.

The virus is then destroyed naturally by the body’s immune system, The London Telegraph reported.

They are expecting results to show that “finding a mass-distributable and affordable cure to HIV is possible”.

Fifteen patients are taking part in the trials, funded with $2.1 million from the Danish Research Council.

If they are found to have successfully been cured of HIV, the new technique will be tested on a wider scale.

Any cure would be affordable for many of the 33 million people worldwide afflicted by the virus.

However, despite the trials Dr. Ole Sogaard, a senior researcher in the department of infectious disease warned that the efficacy in the human body remained unproven.

Medical Daily quoted him as telling the media:

“The challenge will be getting the patients’ immune system to recognize the virus and destroy it. This depends on the strength and sensitivity of individual immune systems.”

British researchers are reportedly conducting similar research through a consortium of five universities.

Both studies are aiming to find a cure for those already infected with the virus and would not result in a preventative measure for HIV or AIDS.
Source: http://www.globalpost.com